JP4559995B2 - Tumor testing device - Google Patents

Description

  The present invention relates to a tumor examination apparatus used when non-invasively detecting a tumor.

  Early detection of cancer is extremely important for the treatment of cancer, and various methods and techniques are used for early detection.

  As one of the means, based on the difference in physical constants (X-ray absorption rate / acoustic impedance) between the main part and the normal part, a region different from the normal part is drawn, and the new blood vessels generated in the region and the surroundings, A morphological diagnosis is known in which the presence or absence of cancer is determined by analyzing the size and shape (such as the smoothness of the surroundings) of fine calcification that occurs inside (for example, Patent Document 1).

  However, such morphological diagnosis largely depends on the experience of doctors and the like, and has various problems in determining whether it is fat or tumor.

Recently, PET cancer cells are capable of finding a fairly small stage (P ositron E mission T omography) test is noted. PET examination is a method of diagnosing cancer cells by injecting glucose (glucose) labeled with an isotope that emits positrons into the body and imaging its distribution with a special camera. In this method, by utilizing the difference in physiological phenomena between cancer cells and normal cells (cancer cells take in more glucose than normal cells), glucose labeled with an isotope is taken into cancer cells, and normal cells It is a method for evaluating cells that emit stronger radiation, and is also referred to as physiological diagnosis (for example, Patent Document 2).

  However, in such a physiological diagnosis, it is difficult to say that injection of glucose labeled with an isotope into the body is harmless to other cellular tissues.

  In addition, as a technique for noninvasively measuring information inside the living body of a subject, the concentration of glucose, hemoglobin, water, etc. in the tissue is optically measured transcutaneously to determine the status of neoplastic disease in the tissue An optical diagnostic technique is known (for example, Patent Document 3). However, since the living body of the subject is composed of a collection of minute regions having different refractive indexes, there is a problem that light is repeatedly scattered strongly, and there is a problem that spatial resolution is lowered. Therefore, technical development for improving sensitivity in such an optical diagnostic technique has been performed.

  In recent years, as a representative example, a technology for improving optical sensitivity by adding correction based on age (hereinafter referred to as age correction) has been published in an academic conference (Non-patent Document 1). This concept of age correction is very effective, and it is said that the sensitivity is actually improved to 90% or more and surpasses other methods.

This concept of age correction is applied to the diagnosis of general tumors. Since the concentration of substances contained in many living organisms is affected by aging, age correction is always required when these are used as tumor markers. At present, in addition to the above-described hemoglobin and the like, many biological substances are used for optical measurement as tumor markers, but all are said to be compounds that require age correction.
JP-A-2005-328507 JP 2005-164609 A Special table 2004-531311 NIH Workshop on Optical Imaging 2004, SPIE

  However, there is a great individual difference in the change in the state due to aging, and there is a problem that sufficient correction cannot be made only by using the actual age. In addition, if the age correction is optional, accurate information supporting the presence of the tumor could not be sufficiently obtained from the concentration of the biological substance. As a result, the sensitivity of tumor detection could not be made sufficiently high, and sometimes the wrong measurement result could be led.

  In view of the above problems, the present invention has no physical damage to the measurement location of the living body, can be measured non-invasively inside the living body, excluding the concept of individual differences due to aging, An object of the present invention is to provide a tumor photodetection device capable of accurately detecting a tumor regardless of age difference.

  The tumor examination apparatus according to the present invention includes a first light having a first wavelength in a light absorption band of glucose and a second light having a second wavelength in a light absorption band of water. Irradiation means for irradiating a region; detection means for detecting light emitted from the living tissue by the irradiation means; and intensity of light at the first and second wavelengths of the emitted light detected by the detection means And calculating means for calculating the concentration distribution of glucose and water in the plurality of regions, and analyzing the concentration distribution to determine a region where the glucose concentration is high and a region where the water concentration is low. And determining means for determining presence / absence of alternately appearing regions.

  There is no physical damage to the measurement site of the living body, and the inside of the living body can be measured non-invasively. Excluding the concept of individual differences due to aging, tumors can be detected accurately regardless of age difference. It is possible to provide a tumor testing apparatus that can perform the above.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. In the following description of the drawings, the same portions are denoted by the same reference numerals, and overlapping descriptions are omitted. The drawings are schematic, and the relationship between the thickness and the planar dimensions, the ratio of the thickness of each layer, and the like are different from the actual ones. Further, there are included portions having different dimensional relationships and ratios between the drawings.

  First, a compound used as a tumor marker will be described.

  In order to play a role as a tumor marker, it is first necessary to be a compound having different concentrations at a normal site and a tumor site in a living tissue. If a compound whose concentration in living tissue is less affected by aging is used as a tumor marker, it is not necessary to perform age correction. Accurate information supporting the presence of can be obtained from tumor markers. “A compound that is not easily affected by aging” means that the concentration in the living tissue hardly changes regardless of age, or the concentration in the living tissue changes with age, but the normal site in the living tissue Refers to a compound whose concentration does not change between the tumor site and the tumor site.

  A specific example of a compound that has different concentrations at normal sites and tumor sites in living tissue and is less susceptible to aging is glucose. As described above, the glucose concentration in tumor cells is always higher than the glucose concentration in normal cells, and this tendency does not change with age. Therefore, if the glucose concentration in the living tissue is optically measured to identify a region having a high glucose concentration, the tumor site can be identified without performing age correction. At this time, the glucose concentration obtained by optical measurement can be used as data supporting the presence of the tumor without performing age correction. In order to examine glucose, it is necessary to use light that matches the light absorption wavelength specific to glucose. Specifically, light absorption at 905 nm, 1450 nm, 1550 nm, 1640 nm, and 2130 nm, which is a combined sound of the vibration mode of glucose, is used.

  It should be noted that the glucose concentration in the tumor changes depending on daily activities such as eating and exercising in the same manner as the glucose concentration in normal tissue. Increasing the glucose concentration ratio between tissues can increase the detection sensitivity of a tumor focused on glucose. Therefore, the difference between the tumor and the normal tissue can be increased by measuring the difference from the measurement result when the water containing sugar (such as sugar water) is ingested and when not ingesting.

  Second, the principle of measurement will be described.

  There are several ways to measure the concentration of a compound present in the area of interest, but by measuring light absorption using a light source with a wavelength characteristic of the compound, it is possible to measure it separately from noise caused by other compounds. It becomes. For example, a decrease in reflected light intensity due to light absorption measures the light intensity itself, so that a measuring device can be assembled with a relatively simple configuration. The light energy accumulated in the compound by light absorption generates heat and acoustic waves. A method of measuring the generated acoustic wave with an acoustic element is called a photoacoustic method, and can use a dynamic range more effectively than absorption measurement for measuring a decrease in light. While it is possible to detect the generated heat as infrared rays, it is also possible to detect a change in temperature as a change in sound velocity of ultrasonic waves.

  In order to measure the position where the compound of interest exists, the position where light enters the body is used as a reference, and a plurality of positions where light (or heat, acoustic waves) are emitted outside the body are set and measured. When the light used is continuous in time (CW light), the position of the absorber is obtained by estimating the statistical light path and calculating the inverse problem using the spatial decomposition method. If the light used changes with time (intensity modulated light, pulsed light), the phase or time delay of the measured light relative to the incident light corresponds to the length of the optical path (optical path length). The position of the absorber is obtained by calculating the inverse problem using this information. Specific device configurations are described in references (for example, visualization technology of biological information, Corona 1997, Phys. Med. Biol. Vol. 50, R1-43, 2005).

  When measuring an acoustic wave, the position where the acoustic wave is generated can be estimated from the speed of sound transmitted through the body. The calculation process described above is repeated for each measurement point, and the absorber is positioned so that there is no contradiction as a whole (Appl. Opt. 39, 5872-83 (2000)). A spatial distribution map is created by assigning the amount of absorber to the position of the absorber thus determined.

  In this way, the compounds distributed in the tumor site are detected using their light absorption, and the concentration and distribution shape are quantitatively compared with the threshold value to distinguish not only the tumor and normal tissue, but also the tumor and benign It is also possible to distinguish tumors. Optical measurement is not affected by radiation exposure. Therefore, by combining with existing medical devices, the diagnostic accuracy can be greatly improved without applying physical burden on the patient.

  Third, a tumor examination apparatus that can determine the presence or absence of breast cancer will be described.

  The inventor has conducted extensive research on cancer, particularly breast cancer. The calcification phenomenon that accompanies the breast cancer formation process is utilized for the detection of breast cancer by focusing on the size and shape of the calcium oxalate or calcium phosphate in the tissue and the distribution relationship with the breast duct structure. It is known that the possibility of breast cancer is increased when fine calcified areas are gathered in the form of dots, or when the area is shaped like a spine (spicula) or distributed along the breast duct. Therefore, it is necessary to measure with high spatial resolution (diagnosis and treatment of breast cancer-latest research trend-Japanese clinical (2000)). Since mammography has a high spatial resolution of 100 μm or less, it is possible to detect the above-described fine calcification region and its shape. In the measurement using light, there is a disadvantage that the spatial resolution becomes low due to multiple scattering, and it is difficult to measure the remarkable calcified region itself. Since calcification occurs in a part of the tissue, it is possible to measure the compound distribution in the peripheral region including the calcification region and indirectly measure the calcification phenomenon from the distribution tendency. While calcification increases the activity of the tumor, normal cells are incapable of metabolic activity, and the constituents are different from those in the tumor that are not calcified. A region containing calcification is characterized by a low water content. Since the thing with a big magnitude | size of calcification is not malignant in many cases, when showing the small calcification suspected of malignancy, the area | region with a low water content is discontinuous. Furthermore, when this discontinuous region shows a distribution along the breast duct, it is highly likely that it corresponds to the extension along the breast duct of breast cancer, and it is possible to detect breast cancer by paying attention to the distribution shape. It becomes possible.

  In view of the characteristics of the above breast cancer, the tumor examination apparatus according to the present invention measures the light absorption distribution of glucose and water, that is, the concentration distribution, respectively, and alternately alternates between regions having a high glucose concentration and regions having a low water concentration. By determining the presence or absence of an appearing region, the presence or absence of the occurrence of breast cancer can be easily evaluated.

  More preferably, in addition to the above apparatus configuration, the light absorption distribution of hemoglobin may be measured simultaneously. It is known that the total amount of hemoglobin increases in cancer tissues because new blood vessels grow and blood flow increases. Therefore, it is possible to detect breast cancer with higher accuracy by determining the presence / absence of a region in which regions having high hemoglobin and glucose concentrations and regions having low water concentrations appear alternately.

  The configuration and operating principle of the tumor examination apparatus of the present invention will be described.

  FIG. 1 shows an example of the tumor inspection apparatus of the present invention. The three types of semiconductor lasers (LD) 2 connected to the function generator 1 emit light having a wavelength that matches the light absorption bands of a plurality of desired measurement substances. In Example 1 below, light having a wavelength matching the light absorption band of hemoglobin reductant, hemoglobin oxidant, and glucose is irradiated. The number of LDs is increased or decreased as appropriate according to the number of substances to be measured. The light irradiated from the LD is overlapped by the optical combiner / coupler 3 and irradiated to the living tissue (biological model sample 5 in the first embodiment) through one optical fiber 4 for light irradiation (irradiation means). In addition, the biological model sample shown in Example 1 is provided with a plurality of grooves 14 for storing model blood, and a thin plate 12 having the same optical constant as that of fat is adhered to the biological model sample. Next, the emitted light obtained from the living tissue (from the living body model sample 5 in the first embodiment) is detected by the OE converter 7 through one optical fiber 6 for light detection (detecting means). By connecting the OE output to the lock-in amplifier 8 and applying an external trigger with the signal to the LD driver 2, the output of each LD can be detected independently. Further, the OE output can be switched to the AC coupling amplifier 9, the signal intensity is amplified by the main amplifier, and then AD-converted by the AD converter 10 and taken into the PC. The optical fiber 4 for light irradiation and the optical fiber 6 for light detection are fixed to one probe 11 with a certain interval. FIG. 2 shows a sectional view of the probe 11. An optical fiber 20 for light irradiation and light detection is disposed inside a metal tube 30, and the tip of the probe is covered with a polymer cap 40.

  Next, the increase / decrease in the intensity of the light in each of the wavelengths of light that match the light absorption bands of the plurality of measurement substances of the emitted light detected by the OE converter 7 is analyzed (analysis means). The above irradiation means, detection means and analysis means are performed in a plurality of regions to be measured, and the increase / decrease in light intensity in the measurement substance in the plurality of measured regions is analyzed, and the plurality of regions in the plurality of measured regions are analyzed. The concentration distribution of the measurement substance is calculated (calculation means). Finally, the concentration distribution is analyzed to determine the presence or absence of a region where the plurality of measurement substances are alternately confirmed (determination means).

  On the other hand, as described above, since the light energy accumulated in the compound by light absorption generates an acoustic wave, the generated acoustic wave can be measured by an acoustic element. When detecting the concentration of a compound by the photoacoustic method, an optical fiber for light irradiation and an acoustic element are arranged as shown in FIG. An optical fiber 4 for light irradiation is installed above the groove 14 for storing the model blood of the biological model sample 5, and the acoustic element 50 is brought into close contact with a surface perpendicular to the light incident surface through an acoustic matching layer. FIG. 3B is a view of the acoustic element 50 of FIG.

  When detecting and measuring acoustic waves, a living tissue is irradiated with light having a wavelength included in the light absorption spectrum region of a plurality of desired measurement substances (glucose, water, hemoglobin) and temporally changing intensity. (Irradiation means) detects an acoustic wave generated from the living tissue (detection means), calculates an acoustic wave generation site from the arrival time of the ultrasonic wave detected by the acoustic element (calculation means), and the acoustic wave A spatial distribution image is configured from the generation site of the acoustic wave and the amplitude value of the acoustic wave, and the spatial distribution value in the inspected part in the spatial distribution image and the spatial distribution value in the normal part in the spatial distribution image are used as threshold values To determine the presence or absence of a tumor at the measurement site (determination means).

  1 to 3 are only examples of the configuration of the tumor testing apparatus of the present invention, and all modes that satisfy the configuration of the present invention are included in the tumor testing apparatus of the present invention.

Example 1
Two types of hemoglobin (oxidized body / reduced body) and glucose were selected as the absorber to be measured. The following model samples were prepared as measurement targets for evaluating the device performance. Using a silicone resin as a base material, a scatterer (10% fat sphere dispersion, product name: Intralipid) and an absorber (colorant for near infrared region, product name: Greenish Green) are dispersed and cured to obtain fat. And the same optical constant (scattering coefficient / absorption coefficient). While a thin plate was prepared by slicing this sample to a thickness of 5 mm to 30 mm (in increments of 5 mm), a groove having a width and length of 5 mm to 25 mm (in increments of 5 mm) and a depth of 5 mm was produced on the block surface. FIG. 5 shows a model sample viewed from above.

  Two types of aqueous solutions were prepared as model blood by selecting pigments each showing a spectrum that matches the absorption spectrum in the near infrared region (around 800 nm) of hemoglobin reductant and hemoglobin oxidant (Model 1: aqueous solution of hemoglobin reductant) Model 2: Aqueous hemoglobin solution). Glucose was added to each model blood at 0 mg / dl to 500 mg / dl (in increments of 100 mg / dl) to obtain model tumor components. Model tumor components were injected with care not to leave air in the grooves made in the block (Model 1 in odd-numbered grooves and Model 2 in even-numbered grooves). A thin plate was carefully placed on the block so that no air layer was formed.

  The measurement wavelength is 760 nm, 840 nm, and 905 nm in combination with the hemoglobin reductant, hemoglobin oxidant, and glucose absorption bands, and three near-infrared LDs as light sources (continuous oscillation LDs are sine waves with frequencies of 500 kHz, 600 kHz, and 700 kHz, respectively). Intensity modulated) was selected. The modulated light output from each LD was combined on a filter, and the sample was irradiated with light through one optical fiber (quartz single core, 250 μm diameter). On the other hand, light is detected by a system (OE detector, which can detect output from sub nW to 10 mW) that transmits outgoing light through an optical fiber (plastic multi-core, 500 μm diameter) and connects a logarithmic amplifier to a high-speed response avalache Si photodiode. did. The distance between the two optical fibers was 3 cm. By connecting the OE output to a lock-in amplifier and applying an external trigger with a signal to the LD driver, the output of each LD can be detected independently. The output from the lock-in amplifier was further amplified by the main amplifier and then AD converted to be taken into the PC.

  First, the light output from each LD was detected with a lock-in amplifier while the probe was placed on the position where there was no groove, and the light intensity passing through the model without the absorber was measured. The current value supplied to the LD was adjusted so that the three LD outputs were of the same level (10 nW to sub-μW level). The probe was rotated around the position of the source fiber until the probe passed over the grooved position and again over the grooveless position. An example is shown in FIG. This corresponds to changing only the position of the detector without changing the position of the light source, and was performed in order to keep the light incident condition as constant as possible. The probe was rotated in 15 degree increments. A value obtained by averaging measured values at 0 degrees and 180 degrees was used as a measurement result when there was no absorber, and a difference between this value and a measurement result at each position was made to correspond to a change derived from absorption.

  For each of the six types of thin plates (thickness 5 mm to 30 mm, in increments of 5 mm), two types of model tumor components (originally having a glucose concentration of 0 mg / dl in 5 groove widths (5 mm to 25 mm, increments of 5 mm)) Model blood) was injected and measured. For all the thin plates, the signal intensity for 760 nm LD in the odd-numbered grooves and 840 nm LD in the even-numbered grooves decreased, and the LD intensity of the other two wavelengths did not change. From this measurement result, it was interpreted that the presence of the corresponding absorber was detected. Although the difference decreased as the groove width decreased from 25 mm to 5 mm, it could be observed separately from noise. Also, as the thickness of the thin plate increased, the intensity of light passing through the groove-free position was significantly reduced, and the current supplied to the LD was increased to increase the light output.

  Next, when the thickness of the thin plate was 15 mm and the width of the groove was 15 mm, a model tumor component having a glucose concentration of 0 mg / dl to 500 mg / dl (in increments of 100 mg / dl) was injected into each groove for measurement. When attention was paid to each LD intensity, the signal intensity for the 760 nm LD and 905 nm LD in the odd-numbered grooves and the 840 nm LD and 905 nm LD in the even-numbered grooves decreased, and no significant change was observed in the signal intensity for the remaining one wavelength LD. As the glucose concentration was increased, the difference of 905 nm LD was increased, but an SN ratio sufficient to determine the function form was not obtained. The effect of glucose concentration did not appear in the difference between the remaining two wavelengths of LD. Further, when the relationship between the groove width and the difference was examined, the difference was reduced when the groove width was reduced, and it was necessary to increase the original LD intensity. When the thickness of the thin plate was increased, the same tendency as when the groove width was decreased was observed.

  By combining these results, it was interpreted that the light absorption derived from glucose can be measured with 905 nm light even in the presence of an oxidized hemoglobin or reduced hemoglobin.

Example 2
The apparatus was evaluated using the same model sample as in Example 1.

  The measurement wavelength is 760 nm, 840 nm, and 1640 nm including the hemoglobin reductant, hemoglobin oxidant, and glucose absorption bands, and three near-infrared LDs (light pulsed with a time width of 10 ns and a repetition frequency of 10 Hz) as light sources. I chose. The modulated light output from each LD was combined on a filter, and the sample was irradiated with light through one optical fiber (quartz single core, 250 μm diameter). On the other hand, an acoustic wave was detected in a state where the acoustic element was brought into close contact with a surface perpendicular to the light incident surface via an acoustic matching layer. The acoustic signal is connected to a lock-in amplifier with an external trigger applied by the signal from the LD driver so that the output of each LD can be detected independently. The output from the lock-in amplifier was further amplified by the main amplifier and then AD converted to be taken into the PC. In addition, in order to monitor the light intensity incident on the sample for each LD, the probe used in Example 1 is used, and the incident light intensity is monitored with a fast response Si photodiode (760 nm and 840 nm) or an InGaAs photodiode (1640 nm). did.

  First, after setting the light irradiation fiber on the position where there is no groove, the light output from each LD is detected by a lock-in amplifier, the light intensity passing through the model without the absorber and the photoacoustic generated from the model The signal was measured. The current value supplied to the LD was adjusted while monitoring the light intensity, so that the three LD outputs were of the same level (10 nW to sub-μW level). Since the photoacoustic signal measured in this state is not synchronized with the three types of LDs, it was interpreted as background noise not derived from a specific absorber.

  The light irradiation fiber was installed on the position with the groove, and after the acoustic elements were brought into close contact with each other in the same relative arrangement as in FIG. 3, the photoacoustic signal was measured. For each of the six types of thin plates (thickness 5 mm to 30 mm, in increments of 5 mm), two types of model tumor components (originally having a glucose concentration of 0 mg / dl in 5 groove widths (5 mm to 25 mm, increments of 5 mm)) Model blood) was injected and measured. For all the thin plates, signal intensity synchronized with the frequency of 760 nm LD in the odd-numbered grooves and 840 nm LD in the even-numbered grooves was observed. From this measurement result, it was interpreted that the presence of the corresponding absorber was detected. As the groove width decreased from 25 mm to 5 mm, the synchronized acoustic signal decreased, but could be observed separately from the background noise. Also, as the thickness of the thin plate increased, the intensity of light passing through the groove-free position was significantly reduced, and the current supplied to the LD was increased to increase the light output.

  Next, when the thickness of the thin plate was 15 mm and the width of the groove was 15 mm, a model tumor component having a glucose concentration of 0 mg / dl to 500 mg / dl (in increments of 100 mg / dl) was injected into each groove for measurement. Focusing on acoustic signals synchronized with each LD frequency, signal intensities synchronized with frequencies of 760 nmLD and 1640 nmLD were observed in the odd-numbered grooves, and 840 nmLD and 1640 nmLD were observed in the even-numbered grooves. As the glucose concentration was increased, the signal intensity synchronized with 1640 nm LD was increased, but an SN ratio sufficient to determine the function shape was not obtained. The effect of glucose concentration did not appear on the signal intensity synchronized with the remaining two wavelengths of LD. Further, when the relationship between the groove width and the difference was examined, when the groove width was reduced, the synchronized signal intensity was reduced, and it was necessary to increase the original LD intensity. When the thickness of the thin plate was increased, the same tendency as when the groove width was decreased was observed.

  By combining these results, it was interpreted that the light absorption derived from glucose can be measured by 1640 nm light even in the presence of a hemoglobin oxidant or a hemoglobin reductant.

Schematic which shows an example of the tumor test | inspection apparatus of this invention. Schematic which shows the probe of the tumor test | inspection apparatus of this invention. Schematic which shows arrangement | positioning of the light irradiation fiber and acoustic element in the tumor test | inspection apparatus of this invention. The figure which showed a mode that the probe of the tumor test | inspection apparatus of this invention was rotated on the model sample. The top view of the model sample of a biological tissue.

Explanation of symbols

1 Function generator 2 LD driver + LD head 3 Optical multiplexer / coupler 4 Optical fiber for light irradiation 5 Biological model sample 6 Optical fiber for optical detection 7 OE converter (photodiode + preamplifier)
8 Lock-in amplifier 9 AC coupling amplifier (+ main amplifier)
10 AD converter + PC
DESCRIPTION OF SYMBOLS 11 Probe 12 Thin plate 13 Model block 14 Model blood groove 20 Optical fiber 30 for light irradiation and light detection Metal cylinder 40 Polymer cap 50 Acoustic element

Claims (6)

Irradiation means for irradiating a plurality of regions of biological tissue with first light having a first wavelength in the light absorption band of glucose and second light having a second wavelength in the light absorption band of water;
Detecting means for detecting light emitted from the living tissue by the irradiation means;
Analyzing the increase and decrease of the light intensity at the first and second wavelengths of the emitted light detected by the detection means, computing means for computing the concentration distribution of glucose and water in the plurality of regions,
A tumor examination apparatus comprising: a determination unit that analyzes the concentration distribution and determines the presence / absence of a region in which a region having a high glucose concentration and a region having a low water concentration appear alternately.   The tumor examination apparatus according to claim 1, wherein the irradiation unit superimposes the first and second lights on the same optical path. A first light having a first wavelength in the light absorption band of glucose, a second light having a second wavelength in the light absorption band of water, and a third light having a third wavelength in the light absorption band of hemoglobin. Irradiating means for irradiating a plurality of regions of biological tissue with
Detecting means for detecting light emitted from the living tissue by the irradiation means;
Analyzing increase / decrease in light intensity at the first, second and third wavelengths of the emitted light detected by the detection means, and calculating concentration distribution of glucose, water and hemoglobin in the plurality of regions Computing means for
A tumor examination apparatus comprising: a determination unit that analyzes the concentration distribution and determines whether or not there is a region in which a region where the glucose concentration and the hemoglobin are high and a region where the water concentration is low appear alternately .   The tumor examination apparatus according to claim 3, wherein the irradiation unit superimposes the first, second, and third lights on the same optical path.   5. The tumor examination apparatus according to claim 1, wherein the measurement unit fixes the irradiation unit and rotates the detection unit. 6. An irradiation means for irradiating a measurement site of biological tissue with a first light having a wavelength of a light absorption band of glucose and a second light having a wavelength of a light absorption band of water;
Detecting means for detecting an acoustic wave generated from the measurement site;
Calculation means for calculating the generation site of the acoustic wave from the arrival time of the ultrasonic wave detected by the detection means;
A spatial distribution image is constructed from the acoustic wave generation site and the acoustic wave amplitude value, and the spatial distribution value in the inspected part in the spatial distribution image and the spatial distribution value in the normal site in the spatial distribution image are used as threshold values. Determining means for comparing each;
A tumor examination apparatus comprising:

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